Compounds having pyridonecarboxylic acid as their basic structure include many compounds known to be useful as synthetic antimicrobial agents since they have excellent antimicrobial potency and wide antimicrobial spectra. Among them, norfloxacin (Patent Literature 1), enoxacin (Patent Literature 2), ofloxacin (Patent Literature 3), ciprofloxacin (Patent Literature 4), and tosufloxacin (Patent Literature 5) have been widely used in clinical settings as therapeutic agents for infections. All of these are agents called new quinolone antimicrobial agents and have been used as therapeutic agents for many infections, such as respiratory, gastrointestinal, or urinary tract infections.
Many resistant microorganisms to these quinolone antimicrobial agents have, however, been reported in recent years and also become a clinical problem (Non-Patent Literature 1 to 2). In particular, the numbers of quinolone antimicrobial agent-resistant methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa are tending to increase (Non-Patent Literature 3 to 4).
Furthermore, antibiotic-associated diarrhea caused by quinolone-resistant Clostridium difficile due to the disturbance of intestinal bacterial flora by the administration of quinolone antimicrobial agents has become a problem (Non-Patent Literature 5 to 6).
As to the mechanism by which various bacteria acquire the drug resistance to such quinolone antimicrobial agents, it has been reported that the decrease in the affinity due to the mutation in the target molecule, type II topoisomerase (DNA gyrase), or pumping of drugs by drug efflux pumps out of the cells lowers effect of the drugs (Non-Patent Literature 7). Therefore, the development of a derivative effective for mutated DNA gyrases or a drug not susceptible to drug efflux pumps has been desired (Non-Patent Literature 8).
Under such situation, the present inventors found a novel derivative in which a 5-amino-2,4-difluorophenyl group and a 3-aminoazetidine ring are introduced at positions 1 and 7 of pyridonecarboxylic acid, respectively (Non-Patent Literature 6).
However, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa exhibiting the resistance to the derivative were found and there has been a problem that the derivative fails to provide enough effect.